Mathematical modeling of helper T lymphocyte/antigen-presenting cell interactions: analysis of methods for modifying antigen processing and presentation

Journal of Theoretical Biology
N G Agrawal, Jennifer J Linderman

Abstract

Helper T lymphocytes (Th cells) are activated by contact with antigen-presenting cells (APCs) that have processed and presented the appropriate MHC-peptide complexes. Two experimental methods for modifying antigen processing and presentation include altering the properties of the antigen and altering the method of antigen uptake. Mathematical modeling was used to investigate the effects of these two methods on the Th cell response. Two mathematical models were used, one for relating the external antigen concentration to the number of MHC-peptide complexes to the number of bound T cell receptors (TCRs) on the Th cell. Large values of MHC/peptide affinity were predicted to compensate for small values of TCR/MHC-peptide affinity in particular parameter ranges. Similarly, large values of antigen receptor number were predicted to compensate for small values of antigen receptor affinity in particular parameter ranges. Results were shown to agree with a variety of experimental data. In addition, model predictions suggest that knowledge of MHC/peptide, TCR/MHC-peptide, and receptor/antigen affinities is not sufficient to accurately describe an experimental system; the kinetic rate constants can dramatically affect antigen processing an...Continue Reading

Citations

Dec 19, 2015·Journal of Immunology Research·Liusong YinTimothy P Hickling
Aug 21, 2014·BioMed Research International·Bárbara de M QuintelaMarcelo Lobosco
Jul 4, 2020·CPT: Pharmacometrics & Systems Pharmacology·Richard J SovéAleksander S Popel
Jul 22, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andreas JanssonPatric Nilsson
Mar 21, 2007·Immunological Reviews·Denise E KirschnerJennifer J Linderman

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